tbuckley/cabot-search huggingface dataset:
Safety and immunogenicity of a simian-adenovirus-vectored rabies vaccine: an open-label, non-randomised, dose-escalation, first-in-human, single-centre, phase 1 clinical trial
Authors: Daniel Jenkin, Adam J Ritchie, Jeremy Aboagye, Sofiya Fedosyuk, Luke Thorley, Samuel Provstgaad-Morys, Helen Sanders, Duncan Bellamy, Rebecca Makinson, Zhi Quan Xiang, Emma Bolam, Richard Tarrant, Fernando Ramos Lopez, Abigail Platt, Ian Poulton, Catherine Green, Hildegund C J Ertl, Katie J Ewer, Alexander D Douglas
Journal: The Lancet Microbe (2022)

BackgroundRabies kills around 60 000 people each year. ChAdOx2 RabG, a simian adenovirus-vectored rabies vaccine candidate, might have potential to provide low-cost single-dose pre-exposure rabies prophylaxis. This first-in-human study aimed to evaluate its safety and immunogenicity in healthy adults.MethodsWe did a single-centre phase 1 study of ChAdOx2 RabG, administered as a single intramuscular dose, with non-randomised open-label dose escalation at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Healthy adults were sequentially allocated to groups receiving low (5 × 109 viral particles), middle (2·5 × 1010 viral particles), and high doses (5 x 1010 viral particles) of ChAdOx2 RabG and were followed up to day 56 after vaccination. The primary objective was to assess safety. The secondary objective was to assess immunogenicity with the internationally standardised rabies virus neutralising antibody assay. In an optional follow-up phase 1 year after enrolment, we measured antibody maintenance then administered a licensed rabies vaccine (to simulate post-exposure prophylaxis) and measured recall responses. The trial is registered with ClinicalTrials.gov, NCT04162600, and is now closed to new participants.FindingsBetween Jan 2 and Oct 28, 2020, 12 adults received low (n=3), middle (n=3), and high doses (n=6) of ChAdOx2 RabG. Participants reported predominantly mild-to-moderate reactogenicity. There were no serious adverse events. Virus neutralising antibody concentrations exceeded the recognised correlate of protection (0·5 IU/mL) in three middle-dose recipients and six high-dose recipients within 56 days of vaccination (median 18·0 IU/mL). The median peak virus neutralising antibody concentrations within 56 days were 0·7 IU/mL (range 0·0–54·0 IU/mL) for the low-dose group, 18·0 IU/mL (0·7–18·0 IU/mL) for the middle-dose group, and 18·0 IU/mL (6·0–486·0 IU/mL) for the high-dose group. Nine participants returned for the additional follow-up after 1 year. Of these nine participants, virus neutralising antibody titres of more than 0·5 IU/mL were maintained in six of seven who had received middle-dose or high-dose ChAdOx2 RabG. Within 7 days of administration of the first dose of a licensed rabies vaccine, nine participants had virus neutralising antibody titres of more than 0·5 IU/mL.InterpretationIn this study, ChAdOx2 RabG showed an acceptable safety and tolerability profile and encouraging immunogenicity, supporting further clinical evaluation.FundingUK Medical Research Council and Engineering and Physical Sciences Research Council.
Research priorities to reduce the impact of musculoskeletal disorders: a priority setting exercise with the child health and nutrition research initiative method
Authors: Zoe Paskins, Clare E Farmer, Fay Manning, David A Andersson, Tim Barlow, Felicity L Bishop, Christopher A Brown, Amanda Clark, Emma M Clark, Debra Dulake, Malvika Gulati, Christine L Le Maitre, Richard K Jones, John Loughlin, Deborah J Mason, Maura McCarron, Neil L Millar, Hemant Pandit, George Peat, Stephen M Richardson, Emma J Salt, E Jane Taylor, Linda Troeberg, Ruth K Wilcox, Elspeth Wise, Colin Wilkinson, Fiona E Watt
Journal: The Lancet Rheumatology (2022)
Quality and Safety in Healthcare, Part LXXVIII
Authors: Jay A. Harolds, Laura B. Miller
Journal: Clinical Nuclear Medicine (2020)

Abstract Numerous expected competencies of a chief nursing officer are outlined in this article including communication, ability to build relationships, expertise about the environment of healthcare and its future directions, leadership, expertise in business matters, combating bullying, encouraging shared decision making, and optimizing interdisciplinary teams and the use of advanced practice providers. These skills are also expected of most other healthcare executives, whether or not they are nurses, because using these competencies increases quality, safety, and value for the patients and improves conditions for the healthcare organization and those who work there.
Quality and Safety in Healthcare, Part LXXVII
Authors: Jay A. Harolds, Laura B. Miller
Journal: Clinical Nuclear Medicine (2020)

The chief nursing officer serves in multiple roles, but among the most important are being the chief administrator for the division of nursing, the chief voice in the organization to engage and empower nurses as professionals, and a major leader for increasing patient satisfaction, quality, and safety. Each of these roles has overlapping responsibilities, and failure in any one of could result in failure in all of them. If all of these roles are done well, the value of the care rendered by the healthcare organization will be substantially increased.
Early-Onset Frontotemporal Dementia-Related Semantic Variant of Primary Progressive Aphasia
Authors: Spyridon Tsiouris, Charalampos Bougias, Spyridon Konitsiotis, Athanasios Papadopoulos, Andreas Fotopoulos
Journal: Clinical Nuclear Medicine (2021)

Abstract Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by cortical and subcortical atrophies, with early involvement of the hippocampus and amygdala. A 58-year-old man with clinical presentation of primary progressive aphasia—particularly its svPPA (semantic variant)—and bilateral asymmetric (left-predominant) anterior temporal lobe atrophy on MRI was referred for brain perfusion SPECT. This revealed bilateral hypoperfusion of the anterior temporal lobe (sustained by software-fused SPECT/MRI), pointing toward FTD rather than Alzheimer disease. Furthermore, voxel-based MRI volumetric analysis confirmed bilateral atrophy affecting the hippocampus and amygdala. Combining SPECT with MRI was supportive of the early-onset FTD-related svPPA diagnosis.
Quality and Safety in Healthcare, Part LXXVI
Authors: Jay A. Harolds, Laura B. Miller
Journal: Clinical Nuclear Medicine (2020)

Abstract Magnet recognition has value that benefits patients; nurses, physicians, and other providers; the healthcare organization; and the community. This includes not only better job satisfaction, more empowerment, and less turnover for nurses, but also better outcomes for patients, more research and evidence-based practice, a superior reputation for the organization, and an easier time recruiting for the organization.
Alpha Before Beta
Authors: Swayamjeet Satapathy, Ashwani Sood, Chandan Krushna Das, Anwin Joseph Kavanal, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2021)

Abstract The utility of β-emitter 177 Lu-DOTATATE in patients of neuroendocrine tumors (NETs) with widespread skeletal metastases is limited by its relatively modest response rates and a significant concern for hematotoxicity. In such situations, targeted α therapy with 225 Ac-DOTATATE can be potentially beneficial. In this report, a 46-year-old man with rectal NET and extensive skeletal metastases was treated upfront with 6 cycles of 225 Ac-DOTATATE at 8 weeks’ intervals. The patient showed excellent symptomatic, biochemical, and radiological response with no grade 3/4 adverse events. The first-line use of 225 Ac-DOTATATE, therefore, presents a novel strategy for metastatic NETs with high skeletal disease burden.
Quality and Safety in Healthcare, Part LXXV
Authors: Jay A. Harolds, Laura B. Miller
Journal: Clinical Nuclear Medicine (2020)

The Magnet Recognition Program® and the Pathway to Excellence® program of the American Nurses Credentialing Center are not only designed to improve the working conditions of nurses, but also to elevate nursing as a profession and ultimately increase quality, safety, and outcomes for patients. There is much overlap in the programs but the Magnet Recognition Program® specifically addresses outcomes and the Pathway to Excellence® program specifically addresses the well-being of nurses.
The “Ultimate Triple PET”
Authors: Matthew McClenathan, Justin G. Peacock
Journal: Clinical Nuclear Medicine (2021)

Abstract A 71-year-old man with a history of carcinoid and prostate adenocarcinoma underwent 68 Ga-DOTATATE PET/CT to evaluate new mediastinal lymphadenopathy. The scan revealed new carcinoid metastases, but the mediastinal nodes were not avid. 18 F-FDG PET/CT was performed to evaluate for cardiac and mediastinal sarcoidosis, revealing a lack of cardiac sarcoidosis, but probable mediastinal sarcoidosis. 18 F-Fluciclovine PET/CT was then performed for possible prostate metastases, revealing the patient’s known prostate cancer. Three different PET radiopharmaceuticals revealed 3 different processes in a single patient within a 195-day period, demonstrating the power of nuclear medicine diagnostics.
Seeing the Invisible
Authors: Tzyy-Ling Chuang, Yu-Ruei Chen, Yuh-Feng Wang
Journal: Clinical Nuclear Medicine (2021)

Abstract A 76-year-old woman with uterine cervical cancer 20 years ago received right total hip replacement 3 months ago for right hip avascular necrosis without specific intraoperative finding. She reported persistent right hip pain after falling from bed. Pelvic x-ray showed right pubic ramus fracture. To evaluate prosthesis loosening, 99m Tc-MDP 3-phase bone scan was arranged, showing diffusely and heterogeneously increased vascularity and tracer perfusion over the right hip, with intensely and heterogeneously increased metabolism in the right iliac bone and hip. SPECT/CT showed nearby swelling of calcified muscles. After debridement and synovectomy, the pathologic report showed chondroblastic osteosarcoma.
Close Association between Altered Urine–Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis
Authors: Osamu Ichii, Marina Hosotani, Md. Abdul Masum, Taro Horino, Yuki Otani, Takashi Namba, Teppei Nakamura, Elewa Yaser Hosny Ali, Yasuhiro Kon
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Tertiary lymphoid structures (TLSs) form in organs exhibiting chronic inflammation. Immune responses to infections, autoimmune responses, or allergic responses may trigger TLS development. We observed urine–urothelium barrier alterations in the renal pelvis of a mouse model and in human subjects with chronic nephritis, with or without infection. Furthermore, urine leaked from the renal lumen into the parenchyma in nephritic mice. This stimulated the production of cytokines/chemokines in renal stromal cells, resulting in TLS development termed “urinary tract–associated lymphoid structures” (UTALSs). UTALS development correlated with chronic nephritis in humans and mice regardless of UTI, thus possibly revealing a novel pathologic mechanism. Elucidation is crucial for better understanding of noninfectious chronic nephritis. Background Kidneys with chronic inflammation develop tertiary lymphoid structures (TLSs). Infectious pyelonephritis is characterized by renal pelvis (RP) inflammation. However, the pathologic features of TLSs, including their formation and association with non-infectious nephritis, are unclear. Methods RPs from humans and mice that were healthy or had non-infectious chronic nephritis were analyzed for TLS development, and the mechanism of TLS formation investigated using urothelium or lymphoid structure cultures. Results Regardless of infection, TLSs in the RP, termed urinary tract–associated lymphoid structures (UTALSs), formed in humans and mice with chronic nephritis. Moreover, urine played a unique role in UTALS formation. Specifically, we identified urinary IFN- γ as a candidate factor affecting urothelial barrier integrity because it alters occludin expression. In a nephritis mouse model, urine leaked from the lumen of the RP into the parenchyma. In addition, urine immunologically stimulated UTALS-forming cells via cytokine (IFN- γ , TNF- α ) and chemokine (CXCL9, CXCL13) production. CXCL9 and CXCL13 were expressed in UTALS stromal cells and urine stimulation specifically induced CXCL13 in cultured fibroblasts. Characteristically, type XVII collagen (BP180), a candidate autoantigen of bullous pemphigoid, was ectopically localized in the urothelium covering UTALSs and associated with UTALS development by stimulating CXCL9 or IL-22 induction via the TNF- α /FOS/JUN pathway. Notably, UTALS development indices were positively correlated with chronic nephritis development. Conclusions TLS formation in the RP is possible and altered urine–urothelium barrier–based UTALS formation may represent a novel mechanism underlying the pathogenesis of chronic nephritis, regardless of urinary tract infection.
Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States
Authors: Andrea R.V.R. Horimoto, Diane Xue, Jianwen Cai, James P. Lash, Martha L. Daviglus, Nora Franceschini, Timothy A. Thornton
Journal: Journal of the American Society of Nephrology (2021)

Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture, such as Hispanic or Latino individuals in the United States. These individuals have an increased risk of CKD.
Decreased vitamin D-binding protein level portends poor outcome in acute-on-chronic liver failure caused by hepatitis B virus
Authors: Daxian Wu, Qunfang Rao, Zhongyang Xie, Xiaoqing Zhu, Yuanmei Che, Jian Wu, Hainv Gao, Jingyu Zhang, Zhouhua Hou, Xiaoyu Cheng, Zeyu Sun
Journal: Clinical and Molecular Hepatology (2022)

Background/Aims: Acute-on-chronic liver failure (ACLF) is a catastrophic illness. Few studies investigated the prognostic value of vitamin D-binding protein (VDBP) for hepatitis B virus (HBV)-related ACLF (HBV-ACLF) resulted in conflicting results.Methods: Two prospective HBV-ACLF cohorts (n=287 and n=119) were enrolled to assess and validate the prognostic performance of VDBP.Results: VDBP levels in the non-survivors were significantly lower than in the survivors (&lt;i&gt;P&lt;/i&gt;&lt;0.001). Multivariate Cox regression demonstrated that VDBP was an independent prognostic factor for HBV-ACLF. The VDBP level at admission gradually decreased as the number of failed organs increased (&lt;i&gt;P&lt;/i&gt;&lt;0.001), and it was closely related to coagulation failure. The areas under the receiver operating characteristic curve (AUCs) of the Child-Pugh-VDBP and chronic liver failuresequential organ failure assessment (CLIF–SOFA)-VDBP scores were significantly higher than those of Child-Pugh (&lt;i&gt;P&lt;/i&gt;&lt;0.001) and CLIF-SOFA (&lt;i&gt;P&lt;/i&gt;=0.0013). The AUCs of model for end-stage liver disease (MELD)-VDBP were significantly higher than those of MELD (&lt;i&gt;P&lt;/i&gt;= 0.0384) only in the case of cirrhotic HBV-ACLF patients. Similar results were validated using an external multicenter HBV-ACLF cohort. By longitudinal observation, the VDBP levels gradually increased in survivors (&lt;i&gt;P&lt;/i&gt;=0.026) and gradually decreased in non-survivors (&lt;i&gt;P&lt;/i&gt;&lt;0.001). Additionally, the VDBP levels were found to be significantly decreased in the deterioration group (&lt;i&gt;P&lt;/i&gt;=0.012) and tended to be decreased in the fluctuation group (&lt;i&gt;P&lt;/i&gt;=0.055). In contrast, they showed a significant increase in the improvement group (&lt;i&gt;P&lt;/i&gt;=0.036).Conclusions: The VDBP was a promising prognostic biomarker for HBV-ACLF. Sequential measurement of circulating VDBP shows value for the monitoring of ACLF progression.
Endoscopy International Open – recently published
Journal: Endoscopy (2022)

Comment on: Efficacy of aggressive hydration with normal saline versus lactated Ringer’s solution for the prevention of post-ERCP pancreatitis in high-risk patients: a randomized controlled trialEndosc Int Open 2022; 10(07): E933-E939DOI: 10.1055/a-1834-6568 Comment on: Epidemiological, clinical and endoscopic characteristics of colorectal neuroendocrine neoplasms: a population-based study in the NetherlandsEndosc Int Open 2022; 10(07): E940-E951DOI: 10.1055/a-1793-9057 Comment on: Integration of robotic in the reprocessing and transfer of endoscopesEndosc Int Open 2022; 10(08): E1022-E1028DOI: 10.1055/a-1789-0532
Commentary
Authors: Hon Chi Yip, Philip Wai-yan Chiu
Journal: Endoscopy (2022)

Endoscopists with enough experience would likely have encountered the horrifying situation of bleeding esophageal varices where the entire endoscopic image was covered by blood. The lack of clear view prevented visualization of the spurting varix and endoscopic variceal ligation would not be possible without a sufficient view of the bleeder. In this issue of Endoscopy, Sekiguchi et al. describe a novel method of gel immersion endoscopy that could improve the endoscopic view for timely variceal rubber band ligation [1]. The unique characteristics of gel act as an ideal medium for visualization of the bleeding from columns of varices. The accurate localization of the variceal bleeding point will certainly improve the success of band ligation and avoid massive hemorrhage leading to liver failure. With the development of specially designed gel for this purpose, it is expected that the gel immersion technique could be applied in more difficult scenarios during luminal therapeutic endoscopy [2] [3].
Biliary aspirate culture: a necessity or a liability?
Authors: Vipul Chaudhari, Rahulkumar Jadhav, Meghraj Ingle
Journal: Endoscopy (2022)

See also: Reply to Chaudhari et al.Endoscopy 2022; 54(08): 833-833DOI: 10.1055/a-1838-4839 See also: Microbiology of bile aspirates obtained at ERCP in patients with suspected acute cholangitisEndoscopy 2022; 54(11): 1045-1052DOI: 10.1055/a-1790-1314
Randomized clinical trial on resection of the primary tumor versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectable metastases.
Authors: Nuh N. Rahbari, Sebastiano Biondo, Manuel Feißt, Thomas Bruckner, Inga Rossion, Steffen Luntz, Ulrich Bork, Markus W. Büchler, Gunnar Folprecht, Meinhard Kieser, Florian Lordick, Juergen Weitz
Journal: Journal of Clinical Oncology (2022)

LBA3507 Background: Systemic chemotherapy improves survival of patients with stage IV colon cancer who are no candidates for curative therapy. However, it has remained controversial, if primary tumor resection prior to chemotherapy further prolongs survival of these patients. We report the combined results of the SYNCHRONOUS and CCRe-IV trial, comparing primary tumor resection followed by systemic chemotherapy to systemic chemotherapy alone in stage IV colon cancer patients. Methods: The SYNCHRONOUS trial (ISRCTN30964555) is a multicentre, randomized, controlled, superiority trial with a two-group parallel design. Colon cancer patients with synchronous unresectable metastases were eligible for inclusion. Exclusion criteria were primary tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy and history of another primary cancer. Resection of the primary tumor as well as systemic chemotherapy was provided according to the standards of the participating institution. The primary endpoint was overall survival (OS) with a minimum follow-up of 36 months (ITT population). An interim analysis yielded a pooled median survival time of 18 months. Assuming a difference of 6 months in median survival (15 vs. 21 months) with a two-sided type I error of 5%, power of 80% and an additional recruitment of 15% the total sample size amounted to n=392 patients (n=196 per arm). In order to accelerate reporting of the primary endpoint, data were pooled with the Spanish CCRe-IV trial (NCT02015923) with similar eligibility criteria, interventions and endpoints. Results: Between September 2011 and March 2013, 393 patients were randomized to primary tumor resection before chemotherapy (PTR; n=187) or chemotherapy alone (CTX; n=206) at 100 centers. The final study cohort included n=295 (75.1%) patients from the SYNCHRONOUS trial and n=98 (24.9%) patients from the CCRe-IV trial. The median follow-up was 36.7 months (95% CI: 36.6-37.3). Median OS was 16.7 months (95% CI: 13.2-19.2) in the PTR arm and 18.6 months (95% CI: 16.2-22.3) in the CTX arm. On final analysis, there was no significant difference for OS (HR 0.95, 95% CI: 0.743-1.215; p-value: 0.685), based on a proportional hazard model (shaired frailty). A total of 45 (24.1%) and 13 (6.4%) patients did not receive any chemotherapy in the PTR and CTX arm, respectively. In line with these data, the number of serious adverse events (excluding postoperative complications) was not different in the CTX arm (44; 20.7%) compared with the PTR arm (24; 12.5%). Conclusions: Resection of the primary tumor before chemotherapy does not prolong OS in patients with newly diagnozed, stage IV colon cancer and synchronous unresectable metastases. Clinical trial information: ISRCTN30964555.
Updated overall survival outcomes in ENZAMET (ANZUP 1304), an international, cooperative group trial of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Ian D. Davis, Andrew James Martin, Robert Richard Zielinski, Alastair Thomson, Thean Hsiang Tan, Shahneen Sandhu, M. Neil Reaume, David William Pook, Francis Parnis, Scott A. North, Gavin M. Marx, John McCaffrey, Raymond S. McDermott, Nicola Jane Lawrence, Lisa Horvath, Mark Frydenberg, Simon Chowdhury, Kim N. Chi, Martin R. Stockler, Christopher Sweeney
Journal: Journal of Clinical Oncology (2022)

LBA5004 Background: The first planned interim analysis of ENZAMET, with 243 deaths after a median follow-up of 34 months, revealed a clinically meaningful overall survival benefit in mHSPC with the addition of enzalutamide to standard of care (hazard ratio 0.67, 95% CI 0.52 to 0.86, p=0.002, Davis et al, NEJM 2019). We now present updated overall survival (OS) findings from the prespecified analysis triggered to occur after 470 deaths. Methods: We randomly assigned participants (pts) with mHSPC to treatment with testosterone suppression (TS) plus either a conventional non-steroidal anti-androgen (NSAA) or enzalutamide. Stratification factors included age, volume of disease (high vs low according to the CHAARTED definition), and planned use of concurrent docetaxel assigned by the treating physician (docetaxel yes vs no). Results: We randomized 1125 pts with a median age of 69 years, including 503 in the docetaxel stratum, and 602 with high volume metastatic disease. OS results in the table below are based on 476 deaths, a median follow-up of 68 months, and a cut-off date of 19JAN2022. The hazard rate for death was 30% lower among all those assigned enzalutamide versus control (p&lt;0.0001). Outcomes by volume status are shown (Table) as well as the subgroups of interest with M1 high or low volume disease at diagnosis selected for concurrent docetaxel. Conclusions: Enzalutamide added to TS, compared with an active comparator of NSAA, provided clinically meaningful improvements in OS for the combined overall cohort, which persisted with an additional 3 years of follow-up. The benefits were more pronounced in pts with low volume disease, and were also seen in the subgroup with M1 high volume mHSPC despite the relatively high survival with TS+docetaxel+NSAA. ENZAMET was led by ANZUP Cancer Trials Group and the University of Sydney NHMRC Clinical Trials Centre, with funding support from Astellas. Clinical trial information: NCT02446405. [Table: see text]